Amyloid Modulation by Nanoparticles in a Phospholipid Environment

It has been established that membranes preform a key role in amyloid aggregation into oligomers and fibrils – a phenomenon which has been identified as the pathology of many diseases. Recently nanoparticles have been examined as a possible treatment for amyloid aggregation. The particles small dimensions enables the penetration of the blood-brain barrier, a property which can be used for therapeutic purposes. Moreover, the prevalence of nanoparticles in many daily used products, necessitates elucidation of their effects on membranes and proteins.

Herein we examine the nature of the interactions between amyloids, membranes and nanoparticles of different types - metallic, semi-conductor and polymeric - through a series of biophysical methods to determine the amyloid fibrillation kinetics, nanoparticle induced protein structure and oligomer state and membrane properties.

Human Islet Amyloid Polypeptide was chosen as a model amyloid and phospholipid small unilamellar vesicles (SUVs) preformed as a cell membrane model.

We show that the particles of modulation activity in amyloid fibrillation is not solely determined by electrostatic forces. Furthermore each particle induces fibrillation through a different pathway resulting in distinct kinetic profiles, amount of fibrils and fibril morphology. Interestingly, the presence of lipid bilayer can change a particle’s activity from acceleration to inhibition.